Non-human mammals, such as rats and dogs, can produce uricase, which converts uric acid into micromolecular allantoin for excretion. Unlike the situation in other mammals, uric acid is the end product of purine metabolism in the human body. Therefore, when concentration of uric acid accumulated in blood is excessively high, hyperuricemia is caused.
Hyperuricemia is a common metabolic disorder, and can cause gout, hypertension, cardiovascular diseases, diabetes mellitus, and renal calculus, which may further lead to nephritis. According to a local epidemiological survey from 1993 to 2008, the prevalence of hyperuricemia is 21.6% in males and is 9.57% in females in Taiwan. At present, hyperuricemia cannot be cured through clinical treatment, but it has been proved that xanthine oxidase inhibitors and uricase are quite effective in reducing the level of uric acid in blood. Treatment of hyperuricemia is not covered by health insurance in Taiwan until symptoms arise. Consequently, health foods that can prevent hyperuricemia or alleviate its symptoms have gained popularity in the health food market.
At present, uricase is mainly produced by using organisms belonging to the genus Aspergillus sp. or Bacillus sp. U.S. Pat. No. 3,669,843 discloses that mutants of Bacillus fastidiosus (NCIB10423, 10424, 10425, 10372) are able to produce uricase when aerobically (220 rpm) cultured at 30° C. for 5 days. U.S. Pat. No. 3,810,820 discloses that bacteria such as Streptomyces cellulosae, S. sulphureus, Bacillus megatherium, B. subtillus, and B. cereus; yeast such as Geotrichum candidum, fungi such as Aspergillus flavus, Asp. oryzae, Asp. tamarii, Asp. luchuensis, Asp. niger, Asp. sydowi, Asp. nidulans, Asp. wentii, Asp. fonsecaeus, Asp. clavatus, Asp. ustus, Asp. ochraceus, Penicillium frequentans, Pen. granulatum, Pen. griseum, Pen. canescens, Pen. spinulosum, Pen. thomii, Pen. waksmani, Pen. raistrickii, Pen. expansum, Pen. purpurescens, Pen. funiculosum, Pen. spiculisporum, Pen. velutinum, Pen. purpurogenum, Pen. spinulosum, Pen. lilacinum, Pen. rubrum, Cephalosporium sp., Alternaria tenuis, A. tenuis, Fusarium solani, Fus. moniliforme, Fus. coeruleum, Fus. oxysporum, Fus. orthoceras, Stemphylium macrosporoideum, Macrosporium apiospermum, Abisidia Glauca+,Mucor mucedo, M hiemalis, M racemosus, Rhizopus arrizus, and Basidiomycete sp. are able to produce unease with average molecular weight of 93,000±3,000 when aerobically cultured with a suitable carbon source, nitrogen source, and uric acid. U.S. Pat. No. 4,987,076 indicates that Bacillus sp. TB-90 (FERM BP-795) is able to produce uricase with molecular weight of 120,000, in which enzyme activity can keep at pH 5 to 9 and 30° C. for 15 days, and the optimum temperature is 45° C. to 50° C. Such strains are also reported in U.S. Pat. No. 4,882,280 to produce uricase in a specific medium. U.S. Pat. No. 5,728,562 indicates that Bacillus sp. TB-90 is able to produce uricase with a specific sequence and molecular weight of 35,000, wherein the uricase is stable in a solution at pH 8.0 and 60° C. for 10 minutes. U.S. Pat. No. 5,955,336 also discloses that Bacillus sp. TB-90 (FERM BP-795) in a host cell of Escherichia coli such as JM109(pKOD316), JM109(pKU1), ISW 1214(pEB2) is able to produce uricase with a specific sequence. U.S. Pat. No. 3,475,276 indicates that Candida utilis 6020 is able to produce uricase when cultured in a medium (5% glucose, 25% asparagine, 1% K2HPO4, 3% MgSO4, 4%(NH4)2SO4) containing uric acid, at pH at least 6.5 and at 15° C. to 35° C. for 8 to 24 hours. U.S. Pat. No. 3,767,533 indicates that novel Corynebacterium uratoxidants nov. sp. U-23(ATCC 21749), U-8(ATCC 21750), U-30(ATCC 21751), and U-31(ATCC 21752) are able to produce uricase when aerobically cultured at pH 5.5 to 9.0 and at 20° C. to 40° C. in the presence of 0.01% to 1.0% uric acid. U.S. Pat. No. 4,062,731 indicates that Micrococcus luteus NRRL B-8166 is able to produce high active uricase of about 1000 U/liter with average molecular weight of 93,000 dalton.
Fermentations and metabolic products are also reported. US 2010/0151063 indicates that barley fermented with fungi or yeast is able to reduce blood uric acid. US 2010/0316618 indicates that metabolic products of Lactobacillus gasseri strain OLL2922 (NITE BP-462) inhibits the increase of blood uric acid and can be used as food or pharmaceuticals. US 2011/0014168 indicates that Lactobacillus gasseri OLL2959(NITE BP-224) and Lactobacillus oris OLL2779(NITE BP-22) are able to digest purine and further inhibit the increase of blood uric acid caused by diet.
However, contamination easily occurs when culturing the above mentioned microorganisms, which requires a long duration of fermentation. Thus, there is need for a novel method to reduce levels of uric acid.